The present disclosure generally relates to antigen-binding proteins (ABPs) that specifically bind to apolipoprotein E (ApoE), compositions comprising such ABPs, methods of using such ABPs, and methods of making such ABPs. In some embodiments, the ABPs provided herein bind lipidated ApoE4. In some embodiments, the lipidated ApoE4 is within a lipoprotein particle, and the ABPs therefore bind to a lipoprotein particle comprising ApoE4. Any suitable ABP may be used. In some embodiments, the ABP is an antibody. In some embodiments, the ABP is an alternative scaffold. The ABPs provided herein may be used for the prevention or treatment of any disease, condition or disorder associated with ApoE4 expression.